Alpha1-Antitrypsin (alpha1-AT) is the major proteinase inhibitor in the human plasma, inhibiting pancreatic elastase, trypsin, chymotrypsin and related proteinases. An important relationship between plasma levels of alpha1-AT and two pathological conditions have been observed in humans: unusually low levels of alpha1-AT are found in the plasma of patients with an adult form of pulmonary emphysema in a childhood form of cirrhosis of the liver. Moreover, an accumulation of alpha1-AT or alpha1-AT-like material have been noted in the livers of these patients, suggesting the glycoprotein is being synthesized but not secreted into plasma. One likely explanation of the problem of transport is the occurrence of abnormality in the attachment and completion of the carbohydrate moiety to the polypeptide chain of alpha1-AT. We have purified, characterized and determined partially the amino acid sequence of alpha1-AT (PiMM) from plasma of normal individuals. We have also studied its mechanism of proteinase inhibitory activity, as well as its survival in animal circulation after removal of sialic acid residues. We propose to perform silimar studies on alpha1-At from normal liver (PiMM) and cirrhotic livers (PiZZ). These studies will include determinations of molecular weight, electrophoretic mobility, isoelectric point, amino acid and carbohydrate compositions, peptide mapping, proteinase inhibitory activities, and survival in plasma. The nature of the bond linking carbohydrate unit(s) to the peptide chain will be studied. Ultimately, the amino acid and carbohydrate sequence will be performed. Characterization of the carbohydrate moiety will be of utmost importance since, as in other glycoproteins, it may be vitally important in the transport or survival of the inhibitor in plasma. From these studies, we hope to gain an insight into the relationship between the function and structure of alpha1-At and thus better understand the pathologies of pulmonary emphysema and cirrhosis of the liver on a molecular level.